Osteoarthritis of the Knee
Conditions
Keywords
osteoarthritis, knee, pain, corticosteroid, intra-articular, injection
Brief summary
The purpose of this study was to evaluate the safety, efficacy and pharmacokinetics of FX006 in patients with osteoarthritis of the knee.
Detailed description
Study FX006-2011-001 was a multi-center, randomized, double-blind, active comparator, parallel-group, single-dose study designed to assess the magnitude and duration of pain relief of three doses (10, 40, and 60 mg) of FX006, an extended-release formulation of TCA, relative to commercially-available TCA IR. The general tolerability of a single injection of FX006 also was assessed. Secondary objectives included exploration of the effect of FX006 on functional improvement, responder status, time to onset of pain relief, global impressions of change, and consumption of analgesic medications and evaluation of the PK profile of single injection of the three dose levels of FX006. The study was planned to be conducted in up to 224 male and female patients ≥40 years of age with OA of the knee enrolled at 22 study centers in the US, Australia, and Canada.
Interventions
DRUGFX006
Single 3 mL intra-articular injection
DRUGTCA IR
Single 1 mL intra-articular injection
Sponsors
Pacira Pharmaceuticals, Inc
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
40 Years to No maximum
Healthy volunteers
No
Inclusion criteria
Main Inclusion Criteria: * Willingness and ability to comply with the study procedures and visit schedules and ability to follow verbal and written instructions * Male or female \>=40 years of age * Diagnosis of unilateral or bilateral OA of the knee for at least 6 months prior to Screening with confirmation of OA according to American College of Rheumatology Criteria for Classification of Idiopathic OA of the Knee (clinical and radiological) based on an X-ray performed within 6 months prior to Screening or during the Screening period * Qualifying mean score on the 24-h average pain score (0-10 numeric rating scale) * Body mass index (BMI) ≤ 40 kg/m2 * Willingness to abstain from use of restricted medications Main
Exclusion criteria
* Ipsilateral hip OA * Fibromyalgia, chronic pain syndrome or other concurrent medical or arthritic conditions which could interfere with the evaluation of the index knee * History of Reiter's syndrome, rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis, arthritis associated with inflammatory bowel disease, sarcoidosis or amyloidosis * History of arthritides due to crystals (e.g., gout, pseudogout) * History of infection in the index joint * Clinical signs and symptoms of active knee infection or crystal disease of the index knee * Presence of surgical hardware or other foreign body in the index knee * Unstable joint (such as a torn anterior cruciate ligament) * IA corticosteroid (investigational or marketed) in any joint within 3 months of Screening * IA hyaluronic acid (investigational or marketed) in the index knee within 6 months of Screening * Oral, inhaled and intranasal corticosteroids (investigational or marketed) within 1 month of Screening * Prior arthroscopic or open surgery of the index knee within 12 months of Screening * Planned/anticipated surgery of the index knee during the study period * Active or history of malignancy within the last 5 years, with the exception of resected basal cell carcinoma, squamous cell carcinoma of the skin, or resected cervical atypia or carcinoma in situ * Insulin-dependent diabetes * Active psychiatric disorder including psychosis and major depressive disorder * History of or active Cushing's syndrome * Any other clinically significant acute or chronic medical conditions (e.g., uncontrolled diabetes) * Skin breakdown at the knee where the injection would take place * Women of child-bearing potential not using effective contraception or who are pregnant or nursing
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change From Baseline to Week 8 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | 8 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Change From Baseline to Week 10 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | 10 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Change From Baseline to Week 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | 12 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8 | 8 weeks | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| WOMAC B (Stiffness Subscale) Change From Baseline at Week 8 | 8 weeks | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| WOMAC C (Function Subscale) Change From Baseline at Week 8 | 8 weeks | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
| Percent of Responders According to OMERACT-OARSI Criteria at Week 8 | 8 weeks | Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. Responders are defined as participants with high improvement in pain or function. |
| Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 8 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | Weeks 8, 10 and 12 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 8 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Patient Global Impression of Change Scores at Week 8 | Week 8 | The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. |
| Clinical Global Impression of Change Scores at Week 8 | 8 weeks | The Clinical Global Impression of Change is a scale that the clinician uses to assess the participants' global function and determine if there has been an improvement or not. The clinician selects one response from the response options that gives the most accurate description of the participant's state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status. |
| Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks. | 8 weeks | — |
| Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 8 weeks | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Weeks 1-7 and Week 9 and 11 | The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine. |
| WOMAC A (Pain Subscale) Change From Baseline at Week 8 | 8 weeks | The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations. |
Countries
Australia, Canada, United States
Participant flow
Recruitment details
This study took place at 22 centers across the United States, Canada and Australia. Enrollment took approximately 7 months.
Pre-assignment details
Subjects were screened within 21 days of being randomized
Participants by arm
| Arm | Count |
|---|---|
| FX006 10 mg Single 3 mL IA injection | 58 |
| FX006 40 mg Single 3 mL IA injection | 59 |
| FX006 60 mg Single 3 mL IA injection | 60 |
| TCA IR (40 mg) Single 1 mL IA injection | 51 |
| Total | 228 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 | FG002 | FG003 |
|---|---|---|---|---|---|
| Overall Study | Adverse Event | 1 | 0 | 0 | 0 |
| Overall Study | missing data | 0 | 1 | 0 | 0 |
| Overall Study | Withdrawal by Subject | 1 | 1 | 1 | 2 |
Baseline characteristics
| Characteristic | FX006 10 mg | FX006 40 mg | FX006 60 mg | TCA IR (40 mg) | Total |
|---|---|---|---|---|---|
| Age, Continuous | 61.5 years | 60.9 years | 61.9 years | 61.6 years | 61.5 years |
| Sex: Female, Male Female | 26 Participants | 31 Participants | 34 Participants | 29 Participants | 120 Participants |
| Sex: Female, Male Male | 32 Participants | 28 Participants | 26 Participants | 22 Participants | 108 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 58 | 0 / 59 | 0 / 60 | 0 / 51 |
| other Total, other adverse events | 13 / 58 | 16 / 59 | 22 / 60 | 22 / 51 |
| serious Total, serious adverse events | 0 / 58 | 2 / 59 | 1 / 60 | 0 / 51 |
Outcome results
Primary
Change From Baseline to Week 10 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 10 weeks
Population: All patients who receive study treatment and have baseline and at least 1 post-dose pain evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | Change From Baseline to Week 10 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | -3.6 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Week 10 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | -3.3 units on a scale | Standard Error 0.31 |
p-value: 0.200290% CI: [-1.1, 0.3]Longitudinal mixed effect model
Primary
Change From Baseline to Week 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 12 weeks
Population: All patients who receive study treatment and have baseline and at least 1 post-dose pain evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | Change From Baseline to Week 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | -3.2 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Week 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | -3.3 units on a scale | Standard Error 0.33 |
p-value: 0.554190% CI: [-0.7, 0.8]Longitudinal mixed effect model
Primary
Change From Baseline to Week 8 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 8 weeks
Population: All patients who receive study treatment and have baseline and at least 1 post-dose pain evaluation.
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | Change From Baseline to Week 8 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | -3.9 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Week 8 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 60 mg vs TCA IR 40 mg | -3.4 units on a scale | Standard Error 0.31 |
p-value: 0.124990% CI: [-1.2, 0.2]Longitudinal mixed effect model
Secondary
Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks.
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks. | 1.0 tablets (1tablet= 500 mg) | Standard Error 0.22 |
| TCA IR 40 mg | Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks. | 1.0 tablets (1tablet= 500 mg) | Standard Error 0.22 |
| TCA IR 40 mg | Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks. | 1.1 tablets (1tablet= 500 mg) | Standard Error 0.22 |
| TCA IR 40 mg | Average Weekly and Total Consumption of Rescue Medications Over 8 Weeks. | 1.2 tablets (1tablet= 500 mg) | Standard Error 0.24 |
Secondary
Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score.
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: Weeks 1-7 and Week 9 and 11
Population: All patients who receive study treatment and have baseline and at least 1 post-dose pain evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 3 | -3.7 units on a scale | Standard Error 0.27 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 11 | -3.7 units on a scale | Standard Error 0.3 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 5 | -3.9 units on a scale | Standard Error 0.28 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 4 | -3.8 units on a scale | Standard Error 0.26 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 7 | -3.9 units on a scale | Standard Error 0.28 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 2 | -3.6 units on a scale | Standard Error 0.27 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 1 | -2.7 units on a scale | Standard Error 0.24 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 6 | -4.0 units on a scale | Standard Error 0.28 |
| FX006 60 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 9 | -3.8 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 5 | -4.3 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 1 | -3.0 units on a scale | Standard Error 0.24 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 2 | -3.9 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 3 | -4.1 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 4 | -4.3 units on a scale | Standard Error 0.26 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 6 | -4.3 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 7 | -4.4 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 9 | -4.2 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 11 | -3.9 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 3 | -4.2 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 5 | -4.2 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 2 | -3.8 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 1 | -3.0 units on a scale | Standard Error 0.24 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 6 | -4.2 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 7 | -3.9 units on a scale | Standard Error 0.27 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 11 | -3.2 units on a scale | Standard Error 0.29 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 9 | -3.7 units on a scale | Standard Error 0.29 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 4 | -4.2 units on a scale | Standard Error 0.26 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 9 | -3.3 units on a scale | Standard Error 0.32 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 7 | -3.3 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 5 | -3.5 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 2 | -3.5 units on a scale | Standard Error 0.29 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 4 | -3.7 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 3 | -3.5 units on a scale | Standard Error 0.29 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 6 | -3.4 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 1 | -3.1 units on a scale | Standard Error 0.26 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 1, 2, 3, 4, 5, 6, 7, 9, and 11 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score. | Week 11 | -3.4 units on a scale | Standard Error 0.32 |
Secondary
Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: Weeks 8, 10 and 12
Population: All patients who receive study treatment and have baseline and at least 1 post-dose pain evaluation.
| Arm | Measure | Group | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|---|
| FX006 60 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 10 Weeks | -3.8 units on a scale | Standard Error 0.29 |
| FX006 60 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 8 Weeks | -3.9 units on a scale | Standard Error 0.28 |
| FX006 60 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 12 Weeks | -3.6 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 10 Weeks | -4.1 units on a scale | Standard Error 0.29 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 8 Weeks | -4.3 units on a scale | Standard Error 0.28 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 12 Weeks | -3.7 units on a scale | Standard Error 0.3 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 8 Weeks | -3.4 units on a scale | Standard Error 0.31 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 12 Weeks | -3.3 units on a scale | Standard Error 0.33 |
| TCA IR 40 mg | Change From Baseline to Each of Weeks 8, 10, and 12 in Weekly Mean of the Average Daily (24-hour) Pain Intensity Score for FX006 10mg and 40 mg vs TCA IR 40 mg | 10 Weeks | -3.3 units on a scale | Standard Error 0.31 |
Secondary
Clinical Global Impression of Change Scores at Week 8
The Clinical Global Impression of Change is a scale that the clinician uses to assess the participants' global function and determine if there has been an improvement or not. The clinician selects one response from the response options that gives the most accurate description of the participant's state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | Clinical Global Impression of Change Scores at Week 8 | 1.9 units on a scale | Standard Deviation 0.16 |
| TCA IR 40 mg | Clinical Global Impression of Change Scores at Week 8 | 1.8 units on a scale | Standard Deviation 0.16 |
| TCA IR 40 mg | Clinical Global Impression of Change Scores at Week 8 | 2.5 units on a scale | Standard Deviation 0.16 |
| TCA IR 40 mg | Clinical Global Impression of Change Scores at Week 8 | 2.6 units on a scale | Standard Deviation 0.17 |
Secondary
Patient Global Impression of Change Scores at Week 8
The Patient Global Impression of Change is a scale that aims to evaluate all aspects of participants' (patients') health and determining if there has been an improvement or not. The participant selects the one response from the response options that gives the most accurate description of his/her state of health (overall status). This is a 7-point scale, and scores range from 1 (Very Much Improved) to 7 (Very Much Worse). Lower scores indicate better health status.
Time frame: Week 8
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | Patient Global Impression of Change Scores at Week 8 | 1.9 units on a scale | Standard Error 0.16 |
| TCA IR 40 mg | Patient Global Impression of Change Scores at Week 8 | 1.8 units on a scale | Standard Error 0.16 |
| TCA IR 40 mg | Patient Global Impression of Change Scores at Week 8 | 2.4 units on a scale | Standard Error 0.16 |
| TCA IR 40 mg | Patient Global Impression of Change Scores at Week 8 | 2.5 units on a scale | Standard Error 0.17 |
Secondary
Percent of Responders According to OMERACT-OARSI Criteria at Week 8
Outcome Measures in Rheumatoid Arthritis Clinical Trials - Osteoarthritis Research Society International. Responders are defined as participants with high improvement in pain or function.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FX006 60 mg | Percent of Responders According to OMERACT-OARSI Criteria at Week 8 | 52 Participants |
| TCA IR 40 mg | Percent of Responders According to OMERACT-OARSI Criteria at Week 8 | 53 Participants |
| TCA IR 40 mg | Percent of Responders According to OMERACT-OARSI Criteria at Week 8 | 47 Participants |
| TCA IR 40 mg | Percent of Responders According to OMERACT-OARSI Criteria at Week 8 | 32 Participants |
Secondary
Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FX006 60 mg | Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 47 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 49 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 48 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >20% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 30 Participants |
Secondary
Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FX006 60 mg | Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 42 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 47 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 45 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >30% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 27 Participants |
Secondary
Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8
The pain intensity score is measured using an 11-point numeric rating scale (NRS), where 0 indicates no pain and 10 indicates pain as bad as you can imagine.
Time frame: 8 weeks
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| FX006 60 mg | Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 35 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 40 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 34 Participants |
| TCA IR 40 mg | Responder Status as Defined by the Proportion of Patients Achieving >50% Improvement From Baseline in the Mean Daily Pain Intensity Scores at Week 8 | 23 Participants |
Secondary
WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8 | -1.2 units on a scale | Standard Error 0.12 |
| TCA IR 40 mg | WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8 | -1.2 units on a scale | Standard Error 0.12 |
| TCA IR 40 mg | WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8 | -1.1 units on a scale | Standard Error 0.11 |
| TCA IR 40 mg | WOMAC A1 (Pain on Walking Question) Change From Baseline at Week 8 | -0.8 units on a scale | Standard Error 0.13 |
Secondary
WOMAC A (Pain Subscale) Change From Baseline at Week 8
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | WOMAC A (Pain Subscale) Change From Baseline at Week 8 | -1.23 units on a scale | Standard Error 0.099 |
| TCA IR 40 mg | WOMAC A (Pain Subscale) Change From Baseline at Week 8 | -1.33 units on a scale | Standard Error 0.098 |
| TCA IR 40 mg | WOMAC A (Pain Subscale) Change From Baseline at Week 8 | -1.16 units on a scale | Standard Error 0.097 |
| TCA IR 40 mg | WOMAC A (Pain Subscale) Change From Baseline at Week 8 | -0.96 units on a scale | Standard Error 0.108 |
Secondary
WOMAC B (Stiffness Subscale) Change From Baseline at Week 8
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | WOMAC B (Stiffness Subscale) Change From Baseline at Week 8 | -1.37 units on a scale | Standard Error 0.113 |
| TCA IR 40 mg | WOMAC B (Stiffness Subscale) Change From Baseline at Week 8 | -1.49 units on a scale | Standard Error 0.112 |
| TCA IR 40 mg | WOMAC B (Stiffness Subscale) Change From Baseline at Week 8 | -1.24 units on a scale | Standard Error 0.111 |
| TCA IR 40 mg | WOMAC B (Stiffness Subscale) Change From Baseline at Week 8 | -0.99 units on a scale | Standard Error 0.124 |
Secondary
WOMAC C (Function Subscale) Change From Baseline at Week 8
The Western Ontario and McMaster Universities (WOMAC®) Osteoarthritis Index is a questionnaire that measures pain, stiffness, and function both independently and collectively, using a Likert 3.1, 5-point scale. The Likert Scale uses the following descriptors for all items: none, mild moderate, severe, and extreme, corresponding to an ordinal scale of 0-4. Higher scores on the WOMAC indicate worse pain, stiffness, and functional limitations.
Time frame: 8 weeks
| Arm | Measure | Value (LEAST_SQUARES_MEAN) | Dispersion |
|---|---|---|---|
| FX006 60 mg | WOMAC C (Function Subscale) Change From Baseline at Week 8 | -1.22 units on a scale | Standard Error 0.096 |
| TCA IR 40 mg | WOMAC C (Function Subscale) Change From Baseline at Week 8 | -1.31 units on a scale | Standard Error 0.096 |
| TCA IR 40 mg | WOMAC C (Function Subscale) Change From Baseline at Week 8 | -1.13 units on a scale | Standard Error 0.095 |
| TCA IR 40 mg | WOMAC C (Function Subscale) Change From Baseline at Week 8 | -0.94 units on a scale | Standard Error 0.106 |